Rapid and persistent decline in soluble CD163 with successful direct-acting antiviral therapy and associations with chronic hepatitis C histology

Scand J Gastroenterol. 2018 Aug;53(8):986-993. doi: 10.1080/00365521.2018.1481996. Epub 2018 Jul 10.

Abstract

Background and aim: Soluble CD 163 (sCD163) is released from activated liver macrophages in chronic viral hepatitis C (HCV) and serum levels reflect liver disease severity. The impact of direct-acting antiviral (DAA)-therapy on sCD163-levels and the ability of sCD163 to predict the presence of liver fibrosis remain unclear. In a combined observational and prospective study, we aimed to investigate changes in sCD163 with DAA-treatment, to investigate associations between sCD163 and histopathological activity and fibrosis and to validate the sCD163-based fibrosis score in HCV-patients.

Methods: We examined three groups of patients: an Australian (n = 28) treated with pegylated-interferon and a first-generation DAA, a Danish (n = 38) treated with sofosbuvir-based DAA-regimens and a Japanese (n = 562) assessed for activity and fibrosis (Metavir scoring system) in liver biopsies. Serum sCD163-levels were quantified by ELISA.

Results: Thirteen (46%) of the Australian patients achieved sustained virological response (SVR) and only these patients had significant decreases in sCD163-levels (2.7 (95%CI:1.9-3.6) vs. 4.1(2.9-5.7) mg L - 1, p = .008). In the Danish group, 37 (97%) patients achieved SVR at 12-weeks post-treatment with 32% reduction in sCD163-levels (5.0 (4.3-5.8) vs. 7.4 (6.3-8.7), p < .001). The decline was rapid and persisted 12 months after treatment cessation (p < .007). sCD163 levels increased in parallel with inflammatory activity and fibrosis (p < .001). The sCD163-based fibrosis score outperformed established fibrosis scores for significant fibrosis (areas under the receiver operating characteristics curves (AUROCs): 0.79 (0.75-0.83) vs. aspartate aminotransferase to platelet ratio index (APRI) 0.73 (0.69-0.77), Fibrosis-4 (FIB-4) 0.74 (0.70-0.78), p < .001).

Conclusion: sCD163-levels decline rapidly with successful DAA therapy and are associated with histological inflammatory activity and fibrosis, confirming a key role for macrophages in HCV inflammation and fibrosis and supporting sCD163 as a biomarker of treatment response.

Keywords: Inflammation; fibrosis; interferon treatment; macrophages; sofosbuvir.

Publication types

  • Multicenter Study
  • Observational Study

MeSH terms

  • Aged
  • Antigens, CD / blood*
  • Antigens, Differentiation, Myelomonocytic / blood*
  • Antiviral Agents / therapeutic use*
  • Aspartate Aminotransferases / blood
  • Biomarkers / blood
  • Cross-Sectional Studies
  • Female
  • Fibrosis
  • Hepatitis C, Chronic / drug therapy*
  • Hepatitis C, Chronic / pathology
  • Humans
  • Internationality
  • Liver / pathology
  • Male
  • Middle Aged
  • Platelet Count
  • Predictive Value of Tests
  • Prospective Studies
  • ROC Curve
  • Receptors, Cell Surface / blood*
  • Sofosbuvir / therapeutic use*
  • Sustained Virologic Response

Substances

  • Antigens, CD
  • Antigens, Differentiation, Myelomonocytic
  • Antiviral Agents
  • Biomarkers
  • CD163 antigen
  • Receptors, Cell Surface
  • Aspartate Aminotransferases
  • Sofosbuvir